The goal of this work is to investigate physiological mechanisms mediating the development and refinement of synapses in the lateral superior olive (LSO). The LSO is a binaural auditory brainstem nucleus whose principal neurons receive excitation and inhibition from distinct nuclear sources. Following a developmental program of functional and anatomical synaptic refinement, excitatory and inhibitory afferents to the LSO are tonotopically organized and frequency matched in the mature rodent. These unique conditions make the LSO a model system for studying how mechanisms of excitatory and inhibitory plasticity may be coordinated to produce appropriately balanced neural circuits. This proposal builds on our preliminary work demonstrating the striking and unexpected necessity of hyperpolarization for long-term potentiation of excitatory synapses in the LSO, and outlines a series of experiments to test mechanisms mediating this novel form of plasticity. PUBLIC HEALTH RELEVANCE: This goal of this project is to provide insight into the cellular mechanisms underlying the formation of precise neuronal connections in the mammalian auditory system. Studying these mechanisms will lead to a better understanding of causes and potential treatments of auditory processing disorders such as developmental dyslexia, speech processing impairments, and autism.